In Silico Study of Neoagaro-Oligosaccharides (NAOS) Anti-Inflammatory Activity: Molecular Docking with iNOS and COX-2 Proteins

Neoagaro-Oligosaccharides (NAOS) arise from the enzymatic hydrolysis of agarose employing β-agarases enzymes. Comprising diverse monomers such as neoagarobiose (NA2), neoagarotetraose (NA4), neoagarohexaose (NA6), and neoagarooctaose (NA8), NAOS are characterised by their Degree of Polymerization (DP). Extensive investigations have delineated the potential of various NAOS monomers, particularly anti-inflammatory agents, owing to their capability to impede iNOS and COX-2, pivotal mediators of inflammation. Nevertheless, the molecular interplay between NAOS and inflammatory mediators remains unexplored. Thus, this study aimed to elucidate the interaction dynamics between NAOS with iNOS and COX-2. Employing ligands neoagarobiose (ID: 275080182), neoagarotetraose (ID: 130476782), neoagarohexaose (ID: 131485243), and neoagarooctaose (ID: 54758640) in conjunction with target proteins iNOS (3E7G) and COX-2 (5F19), analyses were conducted utilising ProTox-II and SwissADME. Protein preparation was carried out using Discovery Studio, while ligand preparation entailed PyRx, with docking facilitated by CBDock2.0. Absorption, distribution, metabolism, and excretion (ADME) evaluations revealed that neoagarobiose, neoagarotetraose, neoagarohexaose, and neoagarooctaose did not adhere to Lipinski’s Rule of Five. Docking simulations exhibited the capacity of all ligands to engage with the binding site of iNOS, forming diverse bond types. Notably, neoagarobiose, neoagarotetraose, and neoagarohexaose demonstrated enhanced affinity towards COX-2, whereas neoagarooctaose exhibited heightened binding affinity towards iNOS. © Universiti Putra Malaysia Press.